This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Manganese redox chemistry is fundamental to biological processes at molecular,cellular and environmental scales, from antioxidant defense to oxygenicphotosynthesis. Biomedically important enzymes including Mn superoxide dismutase(MnSOD), Mn catalase (MnC), and oxalate oxidase (OXO) require a catalytic manganesecofactor for their biological function, yet the molecular mechanisms involved indelivering the essential metal ion are just beginning to be studied in detail. The goal of this project is to advance our understanding of the biochemicalmechanisms responsible for the metal-binding maturation of the ubiquitous andessential antioxidant metalloezyme, MnSOD. This work is fundamental to understandingthe role of manganese trafficking in human health and disease. Further,understanding the metal binding mechanism of this Mn metalloenzyme may contributenew insight into biological defenses against oxidative stress, a key factor in agingand neurodegenerative disorders. This work may also shed light on diseases of metalhomeostasis in which metal misincorporation occurs.